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Molecular and Cellular Biology, August 1999, p. 5247-5256, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Mutations in Translation Initiation Factors Lead to
Increased Rates of Deadenylation and Decapping of mRNAs in
Saccharomyces cerevisiae
David C.
Schwartz1 and
Roy
Parker1,2,*
Department of Molecular and Cellular
Biology1 and Howard Hughes Medical
Institute,2 University of Arizona,
Tucson, Arizona 85721
Received 25 January 1999/Returned for modification 11 March
1999/Accepted 23 April 1999
The turnover of most mRNAs in Saccharomyces cerevisiae
begins with deadenylation followed by decapping and 5'
3'
exonucleolytic digestion. An important question involves the mechanisms
that allow particular mRNAs to exhibit different rates of both
deadenylation and decapping. Since the cap structure plays a critical
role in the assembly of translation initiation factors, we hypothesized that the status of the cytoplasmic cap binding complex would affect the
rate of decapping. To test this hypothesis, we examined mRNA decay
rates in yeast strains that were defective in several translation initiation factors that are part of the cap binding complex. These experiments yielded three significant observations. First, any mutation
known to inhibit translation initiation also increased the rate of
decapping. Second, decapping still occurred only after deadenylation,
suggesting that the ability of the poly(A) tail to inhibit decapping
does not require efficient translation of the transcript. Third,
mutants with defects in translation initiation factors also showed an
increase in the rate of deadenylation, suggesting that the rate of
deadenylation may be controlled primarily by the translation status of
the transcript. These results argue that the nature of the translation
initiation complex is a critical factor in determining the mRNA
half-life. This view also implies that some cis-acting
sequences that modulate mRNA decay rate do so by affecting the
translation status of the transcript.
*
Corresponding author. Mailing address: Howard Hughes
Medical Institute, University of Arizona, Tucson, AZ 85721. Phone:
(520) 621-9347. Fax: (520) 621-4524. E-mail:
rrparker{at}u.arizona.edu.
Molecular and Cellular Biology, August 1999, p. 5247-5256, Vol. 19, No. 8
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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